Effects of tandamine and pirandamine, new potential antidepressants, on the brain uptake of norepinephrine and 5-hydroxytryptamine and related activities

Abstract

Two novel agents, tandamine [TA; a thiopyrano (3,4-b) indole] and pirandamine [PA; an indeno (2,1-c) pyran], and the tricyclic antidepressants desimipramine (DMI), imipramine (I) and amitriptyline (A) were compared in various in vivo pharmacological tests and for norepinephrine (NE) and 5-hydroxytryptamine (5-HT) neuronal uptake inhibition. TA was found to be equivalent, or greater, in activity to DMI in blocking brain NE uptake, antagonizing reserpine-induced effects and potentiating the behavioural effects of l-Dopa. Similarly to DMI, TA did not appreciably block brain 5-HT uptake; unlike DMI, TA did potentiate central 5-HT activity at high doses. PA exerted an opposite profile to TA, being equivalent to A and greater than I as a 5-HT uptake blocker and central 5-HT potentiator; PA was not effective as a NE uptake blocker or potentiator. Neither TA or PA exhibited in vivo MAO inhibition, and in contrast to DMI, I and A, exhibited no central anticholinergic effects. TA, but not PA, potentiated apomorphine-induced gnawing. These findings indicate that TA is a relatively specific blocker of neuronal NE uptake and PA is a selective 5-HT uptake blocker.